Key Laboratory of Water Environment Evolution and Pollution Control in Three Gorges Reservoir, School of Environmental and Chemical Engineering, Chongqing Three Gorges University, Chongqing 404100, China.
State Key Laboratory of Chemical Engineering and School of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China.
ACS Appl Mater Interfaces. 2021 Jan 13;13(1):123-134. doi: 10.1021/acsami.0c16688. Epub 2020 Dec 13.
By combining large-scale dissipative particle dynamics and steered molecular dynamics simulations, we investigate the mechanochemical cellular internalization pathways of homogeneous and heterogeneous nanohydrogels and demonstrate that membrane internalization is determined by the crosslink density and encapsulation ability of nanohydrogels. The homogeneous nanohydrogels with a high crosslink density and low encapsulation ability behave as soft nanoparticles partially wrapped by the membrane, while those with a low crosslink density and high encapsulation ability permeate into the membrane. Regardless of the crosslink density, the homogeneous nanohydrogels undergo typical dual morphological deformations. The local lipid nanodomains are identified at the contacting region between the membrane and nanohydrogels because of different diffusion behaviors between lipid and receptor molecules during the internalization process. The yolk@shell heterogeneous nanohydrogels present a different mechanochemical cellular internalization pathway. The yolk with strong affinity is directly in contact with the membrane, resulting in partial membrane wrapping, and the contacting area is much reduced when compared to homogenous nanohydrogels, leading to a smaller lipid nanodomain and thus avoiding related cellular toxicity. Our findings provide a critical mechanism understanding of the biological pathways of nanohydrogels and may guide the molecular design of the hydrogel-based materials for controlled release drug delivery, tissue engineering, and cell culture.
通过结合大规模耗散粒子动力学和导向分子动力学模拟，我们研究了均相和异相纳米水凝胶的机械化学细胞内化途径，并证明了膜内化由纳米水凝胶的交联密度和包封能力决定。交联密度高、包封能力低的均相纳米水凝胶表现为部分被膜包裹的软纳米颗粒，而交联密度低、包封能力高的纳米水凝胶则渗透到膜中。无论交联密度如何，均相纳米水凝胶都会经历典型的双重形态变形。在纳米水凝胶与细胞膜相互作用的区域中，由于在内化过程中脂质和受体分子的扩散行为不同，会产生局部脂质纳米区。蛋黄@壳型异相纳米水凝胶表现出不同的机械化学细胞内化途径。具有强亲和力的蛋黄直接与细胞膜接触，导致部分膜包裹，与均相纳米水凝胶相比，接触面积大大减少，导致脂质纳米区更小，从而避免了相关的细胞毒性。我们的发现为纳米水凝胶的生物学途径提供了重要的机制理解，并可能指导基于水凝胶的材料的分子设计，以实现可控释放药物传递、组织工程和细胞培养。
